Xechem proposes to examine antimicrobial, antifungal, antivira1 and immunomodulatory activities in biological extracts derived from Rutgers University collection of deep-sea hydrothermal vent and sulfide/methane seep organisms in collaboration with marine scientists at Rutgers. This presents a unique opportunity for natural products screening from organisms that live in some of the most extreme environments on this planet, such as high temperatures, great pressures, and strong concentrations of toxic chemicals and radionuclides. Primary biological production in these unusual communities is based on chemosynthesis rather than photosynthesis. In Phase I of the project extracts of 50-l00 marine extremophiles will be examined in l0 Gram positive and Gram negative bacteria, 3 fungal organisms, and 5 viruses representing different virus families. In addition, a screen for an immunomodulating activity will also be performed. Extracts displaying desired activity in these screens will be subjected to bioassay-guided fractionation in Phase II of the Project to isolate and structurally characterize pure biologically active compounds, and initiate in vivo testing of activity. Determining the structures of the active molecules and understanding the mechanisms and pathways used by these organisms to degrade, detoxify, tolerate, or otherwise avoid these compounds may have profound implications for the prevention and treatment of various diseases. PROPOSED COMMERCIAL APPLICATIONS: Rutgers marine biologists have characterized at the molecular level more than two hundred vent and seep species, many new to science. Our collaborative search for antimicrobial, antifungal, antiviral and immunomodu1atory activity in this unique biota may provide many new classes of compounds that have no counterparts in terrestrial plants or animals.